Lipid modulation of membrane-bound epitope recognition and blocking by HIV-1 neutralizing antibodies.
The conserved, aromatic-rich membrane-proximal external region (MPER) of gp41 is functional in human immunodeficiency virus (HIV)-cell fusion by perturbing membrane integrity. Broadly-neutralizing 2F5 and 4E10 monoclonal antibodies (MAb-s) recognize amino- and carboxy-terminal epitope sequences within this domain, respectively. An MPER peptide overlapping 2F5 and 4E10 epitope sequences was capable of breaching the permeability barrier of lipid vesicles. Cholesterol and sphingomyelin raft-lipids, present at high quantities in the HIV-1 envelope, promoted exposure or occlusion of 4E10 epitope, respectively. Conversely, 2F5 epitope accessibility was affected to a lesser extent by these envelope lipids. These observations support the idea that MPER epitopes on membranes are segmented in terms of how they are affected by envelope lipids, which may have implications for MPER-based vaccine development.
Huarte
Nerea
N
Biophysics Unit (CSIC-UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.
Lorizate
Maier
M
Kunert
Renate
R
Nieva
José L
JL
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic; D000911:Antibodies, Monoclonal / Q000276:immunology; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000737:chemistry / Q000276:immunology; D017124:Conserved Sequence; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D008561:Membrane Fusion; D021962:Membrane Microdomains / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D017434:Protein Structure, Tertiary; D013109:Sphingomyelins / Q000737:chemistry / Q000276:immunology; D053835:Unilamellar Liposomes
D016915:AIDS Vaccines; D024322:Amino Acids, Aromatic; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D016056:Immunodominant Epitopes; D010455:Peptides; D013109:Sphingomyelins; D053835:Unilamellar Liposomes; D002784:Cholesterol